Abstract:

The Alzheimer's Disease Neuroimaging Initiative in Japan (J-ADNI) project has been launched enacting
a harmonized protocol with US and worldwide ADNI studies. Thirty-eight clinical sites recruited a total of
600 subjects: 300 mild cognitive impairment (MCI), 150 Alzheimer's disease (AD) and 150 cognitively normal (CN),
and candidates of surrogate markers such as MRI, FDG-PET, PiB-PET, BF227-PET and CSF biomarkers are being
accumulated. Among the registered 311 subjects, as of February 2010, amyloid PET was acquired in 45%, and
FDG-PET was obtained in 75% of the total participants.

The first 75 baseline PiB scans from 9 PET centers were analyzed with demographic information including APOE
genotype. A bolus injection of [C-11] PiB (537±70 MBq) was followed by a 70-min 3D dynamic scan. A sum
image of 50-70 min and a parametric image of distribution volume by Logan graphical analysis were created in
each subject, and evaluated in reference to the cerebellar cortex measures, that is SUVR and DVR, for both visual
diagnosis and quantitative measurements of neocortical regions.

We estimated an optimal cut-off value for SUVR as 1.47, with which the discrimination well corresponds to the
visual diagnosis. The prevalence of PiB positivity was 93% in AD (age and ratio of APOE4 carrier; 73±5.3, 50.0%),
70% of MCI (71±5.6, 57.9%), and 32% of CN (67±5.1, 43.8%). The PiB positive ratio in APOE4 carrier in AD,
MCI and CN groups were 100%, 100%, and 54%, whereas those in non-carriers remain 88%, 40%, and 22%.
A significant positive effect of APOE4 for PiB accumulation was observed even in early 60s. Among 3 cases out
of 33 subjects diagnosed as PiB-negative with SUVR images, we found distinct cortical deposition of PiB in DVR
images, but none of the reverse.

We observed a PiB positive ratio in the Japanese population equivalent to the US, Australia and EU studies.
A significant APOE4 effect was found to push up amyloid-beta deposition even in young-old subjects. A dynamic PiB-PET analysis may give us more sensitive assessment for a small amount of amyloid deposition.